tbuckley/cabot-search huggingface dataset:
Abstract 9506: Calpain Activation in Early Reperfusion Triggers Pyroptosis Resulting in Myocardial Ischemia/Reperfusion Injury
Authors: Michael V Cohen, Ximing Yang, Sarah Sayner, Jonathon Audia, James Downey
Journal: Circulation (2022)

Sterile inflammation contributes to reperfusion injury. During myocardial ischemia/reperfusion (I/R), inflammasomes proteolytically activate caspase-1 (cas-1) which then kills cardiomyocytes by liberating N-terminal fragments of gasdermin D which form large pores in the sarcolemma (pyroptosis). We and others find hearts from cas-1 knockout (KO) mice have less myocardial infarction (MI) after I/R than those of wild type (WT) hearts. Pharmacologic cas-1 blockade when administered prior to ischemia or at the onset of reperfusion provides similar protection against MI but protection is lost when blockade is started 10min after reperfusion revealing that cas-1 does its killing in the first 10min of reperfusion. We wondered what could trigger cas-1 activation at reperfusion. Ca ++ floods myocytes at reperfusion making Ca ++ a suspect. We tested if adenyl cyclase isoform 10 (AC10), which is stimulated by Ca ++ and in one study promoted I/R injury in cardiomyocytes, could be responsible. However, there were no differences in infarct size among AC10 -/- KO, AC10 -/+ heterozygous, and WT buffer-perfused mouse hearts after 50min global ischemia/2h reperfusion. Ca ++ also activates calpain which releases membrane-bound inactive procas-1 which is required for infammasome assembly. Adding calpain antagonist calpeptin (CPT) to the perfusate of isolated AC10 -/+ hearts reduced MI from 90% of risk zone to 55% (p&lt;0.001). Cas-1 KO mouse hearts were similarly protected after I/R (40% infarction) and treating KO hearts with CPT resulted in no added protection suggesting both cas-1 and calpain are steps in the same mechanism of cell killing. This result was amplified by lack of added protection when mice received combined CPT and emricasan (EMRI), a pan-cas blocker. In contrast, EMRI plus preconditioning does give additive protection. Hence calpain activity in the initial minutes of reperfusion is also involved in injurious pyroptosis and may be a viable target in treatment of acute MI.
Abstract 9764: Simultaneous Assessment of Coronary Flow Reserve and Left Ventricular Strain During Vasodilator Stress Measured by <sup>13</sup> N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging
Authors: Takatoyo Kiko, Keiichiro Endo, Kenji Fukushima, Yasuchika Takeishi
Journal: Circulation (2022)

Introduction: Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) is able to yield important information regarding molecular and functional imaging in a one-stop examination. The aim of this study was to investigate the relationship between coronary flow reserve (CFR) and left ventricular longitudinal strain (LVLS) using simultaneous acquisitions on hybrid 13 N-ammonia PET/MRI. Methods: Thirty-eight patients with suspected coronary artery disease (CAD) who underwent 13 N-ammonia PET/MRI were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. CFR was calculated from dynamic acquisition of 13 N-ammonia PET. LVLS was evaluated by feature-tracked MRI. Myocardial flow reserve (MFR) and LVLS values were based on a 17-segment model and three coronary territories, left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA). Results: We analyzed 577 myocardial segments in the left ventricle. LVLS under vasodilator stress was significantly increased compared with LVLS at rest in myocardial segments with MFR ≥2.0 (P&lt;0.01), whereas there were no changes between LVLS under stress and LVLS at rest in the segments with MFR &lt; 2.0 (P=0.24). Similarly, regional values of LVLS under vasodilator stress were significantly increased compared with those measured at rest in the coronary territories of LAD (P&lt;0.01), LCx (P&lt;0.01), and RCA (P&lt;0.01) with MFR ≥ 2.0, whereas there were no differences between LVLS at rest and LVLS under stress in those territories with CFR &lt; 2.0 (P=0.45). These data revealed that left ventricular strain under vasodilator stress was impaired in segments with lower CFR. Conclusion: Simultaneous assessment of regional CFR and LV strain was feasible using by 13 N-ammonia PET/MRI. 13 N-ammonia PET/MRI was able to detect not only impaired CFR but also morphological abnormalities, which may improve diagnostic and predictive capacity in patients with CAD.
Abstract 9736: Steerable versus Non-Steerable Sheath Technology in Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis
Authors: Mohammed Mhanna, Azizullah Beran, Ahmad Al-Abdouh, Omar Sajdeya, mahmoud Barbarawi, Mahmoud Alsaiqali, Ahmad Jabri, Ahmad Al-Aaraj, Abdulmajeed Abdullah Alharbi, Paul Chacko
Journal: Circulation (2022)

Introduction: Catheter placement and stability are well-known challenges in atrial fibrillation (AF) ablation. As a result, steerable sheaths were developed to improve catheter stabilization and maintain proper catheter-tissue contact. The purpose of this systematic review and meta-analysis is to see if employing a steerable sheath influences procedure outcome. Method: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of Steerable Sheaths (SS) compared to Non-Steerable Sheaths (NSS) in AF ablation. The primary outcome was the rate of atrial arrhythmia (AA) freedom by the time of the last follow-up. The secondary outcomes were the procedure-related complications and procedural characteristics. Risk ratio (RR) or the mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. Results: A total of 10 studies, including 967 AF patients (mean age: 59.2±11.1 years, 516 patients managed with SS vs. 454 with NSS), were included. SS group showed a higher rate of freedom of AA compared to NSS (RR: 1.19; 95% CI 1.09, 1.29; P &lt; 0.001). Both techniques had similar rate for procedural-related complication (RR: 1.09, 95% CI 0.50, 2.39; P = 0.83). The SS strategy had a shorter procedure time (MD -10.6 (min.), 95% CI -20.97, -0.20; P = 0.05) but comparable fluoroscopic and radiofrequency application times to the NSS group. Conclusions: The steerable sheaths for AF catheter ablation not only reduced the total procedure time but also significantly increased the rate of successful ablation while maintaining a similar safety profile when compared to the traditional non-steerable sheaths.
Abstract 9562: High Sensitivity C Reactive Protein and Recurrence After Catheter Ablation for Atrial Fibrillation: A Meta-Analysis
Authors: Surachat Jaroonpipatkul, Angkawipa Trongtorsak, Jakrin Kewcharoen, Sittinun Thangjui, Issaree Bunyawannukul, Apichai Pokawattana, Leenhapong Navaravong
Journal: Circulation (2022)

Introduction: The recurrence after atrial fibrillation (AF) ablation is not uncommon. High sensitivity C reactive protein (hs-CRP) is one of the widely used inflammatory markers. We conducted meta-analysis to find association between hs-CRP levels and AF recurrence after ablation. Hypothesis: Higher level of high sensitivity C reactive protein (hs-CRP) may predict the rate of AF recurrence. Methods: We searched PubMed, Embase and Wiley-Cochrane library from inception to January 1, 2022. Overall and subgroup analyses were performed. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate the associations between hs-CRP levels and post-ablation AF recurrence. Statistical analysis was performed with Stata 14.0. The primary endpoint of this study is to investigate the association of AF recurrence after catheter ablation and hs-CRP levels. Results: We identified ten studies and total 789 patients were included (299 recurrent vs 490 non-recurrent patients). The mean age was 57.7 years (76.4 % male). There was no different in baseline hs-CRP levels between AF recurrence and non-recurrence groups (WMD = 0.05, 95% CI = -0.04-0.15, p = 0.045). However, higher follow-up CRP levels after ablation was associated with higher AF recurrence (WMD = 0.09, 95% CI = 0.03-0.15, p &lt;0.001)(Figure 1 and 2). Conclusions: Higher post ablation hs-CRP level was associated with more AF recurrence. Hs-CRP may play a role as predictor of AF recurrence.
Abstract 9317: Variability in Non-Vitamin K Oral Anticoagulant Dose Adjustment According to Renal Formulae and Clinical Outcomes in Atrial Fibrillation Patients: Insights From ORBIT-AF II
Authors: Ren Jie Robert Yao, DaJuanicia Holmes, Jason Andrade, Adeera Levin, Jonathan P Piccini, Christopher Fordyce
Journal: Circulation (2022)

Background: Non-Vitamin K Oral Anticoagulants (NOACs) require dose adjustment based on kidney function. Glomerular filtration rate (eGFR) is most commonly used in clinical practice, but product monographs recommend the use of Cockcroft-Gault creatinine clearance equation (eCrCl) for dose adjustment. We sought to evaluate misclassification of NOAC renal dosing using eGFR versus eCrCl. Methods: We included patients enrolled in the ORBIT-AF II trial. eGFR was calculated using both the MDRD and CKD-EPI formulae. Dose adjustments and eligibility were based on landmark trials. Dosing was considered inappropriate when use of eGFR resulted in a lower (under-treatment) or higher (over-treatment) dose than that recommended by eCrCl. Agreement in NOAC dosing between eCrCl and eGFR was assessed. The primary outcome of major adverse cardiovascular and neurological events (MACNE) was a composite of cardiovascular death, stroke or systemic embolism, and myocardial infarction. Sensitivity analysis was performed for the subgroup of patients with CKD (eCrCl&lt;60 ml/min). Results: Among 8,727 in the overall cohort, agreement between CrCl and eGFR was observed in 93.5-93.8% of patients. Among 2,184 patients with CKD, the agreement between eCrCl and eGFR was 79.9-80.7%. Dosing misclassification was observed in 11.5% of rivaroxaban and 1.1% of dabigatran and apixaban treated patients. Patients receiving an inappropriate NOAC dose had a lower mean eCrCl and eGFR. Undertreated patients were older and of lower body weight compared to overtreated and appropriately dosed patients. Dosing misclassification was more frequent in the CKD population (41.9% of rivaroxaban, 5.7% of dabigatran and 4.6% apixaban patients). At one-year, undertreated patients in the CKD group had significantly greater MACNE [adjusted HR 2.90 (1.09-7.75) compared to appropriate NOAC dosing group p = 0.03]. Conclusions: The prevalence of NOAC dosing misclassification NOACs was high when using eGFR, particularly among those with CKD. Among patients with CKD, potential undertreatment due to inappropriate and off-label renal formulae may result in worse clinical outcomes. These findings highlight the importance of using eCrCl, and not eGFR, for dose-adjustment in all AF patients receiving NOACs.
Abstract 314: Changes In The Hounsfield Unit Proportion Of Head Computed Tomography With Time And Neurological Outcomes In Out-of-hospital Cardiac Arrest Survivors
Authors: Yong Nam In
Journal: Circulation (2022)

Changes in the Hounsfield Unit proportion of head computed tomography with time and neurological outcomes in out-of-hospital cardiac arrest survivors Aim: We compared changes in Hounsfield Unit proportion (HUp) with neurological outcomes using head computed tomography (HCT) obtained before and after targeted temperature management of out-of-hospital cardiac arrest (OHCA) survivors. Methods: This retrospective observational study included adult comatose OHCA survivors who underwent HCT scans within 6 h (first HCT) and 72-96 h (second HCT) after the return of spontaneous circulation (ROSC). Automated quantitative analysis using non-enhanced HCT images was applied to identify the difference in HU value distribution across the intracranial area between neurological outcomes. Each pixel in an HCT image has a certain HU level, λ, which is between 1 and 79 in this study. The proportion (%) of λ in a CT image is 0 to 100, with the sum of every λp as 100, as per the definition of λp. The primary outcome was the 6-month poor (CPC 3-5) outcome. Results: Of the 41 included patients (30 males; 73%), 14 (34%) had poor outcomes. In the first HCT, only HU = 29-30 showed a difference according to the neurological outcome; however, in the second HCT, HU = 1-12, 22-33, 39-50 showed a difference ( P &lt; 0.05) (Fig. 1). Among them, the greatest difference between the good and poor neurological outcome groups was the proportion of pixels with HU = 22-33, and the average values were 36.0 ± 6.0 and 43.6 ± 8.1, respectively ( P &lt; 0.01). In addition, receiver operating characteristic analysis showed that the of the second HCT was predictive of prognostic performance from poor neurological outcomes six months after ROSC to moderate to good (0.76; 95% confidence interval, 0.60-0.88). Conclusions: The proportion of in total cerebral regions in HCT scans obtained between 72-96 hours after ROSC in OHCA survivors was associated with poor neurological outcomes six months after ROSC.
Abstract 9381: Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes
Authors: Thomas C Gilliland, Yuxi Liu, Reza Mohebi, Hannah Miksenas, Sara Haidermota, Megan Wong, Xingdi Hu, Joaquim Cristino, Auris Browne, Jorge Plutzky, Sam Tsimikas, James L Januzzi, Pradeep Natarajan
Journal: Circulation (2022)

Introduction: Lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) are independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs together predict coronary artery disease (CAD) severity and outcomes is unclear. We measured Lp(a) isoform-independent particle number and OxPLs associated with apolipoprotein(a) [OxPL-apo(a)] and apolipoprotein-B (OxPL-apoB) among participants in CASABLANCA (ClinicalTrials.gov NCT00842868), a contemporary cath-based registry, and assessed angiographic CAD at baseline and CV events in follow-up. Methods: In 1098 participants undergoing baseline coronary angiography, logistic regression estimated odds of any CAD (≥1 severe coronary stenosis) or multi-vessel CAD (≥2 severe coronary stenoses). Cox proportional hazards regression estimated risk of major adverse cardiovascular events (MACE: non-fatal MI, non-fatal stroke, CV death, or coronary revascularization) over median 4.2 years. Models were adjusted for age, sex, medical history, cholesterol, smoking, and statin use. Results: Median [IQR] Lp(a) was 26.45 nmol/L [11.39-89.49]. Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R≥0.91 for all pairwise combinations). Biomarkers were not associated with any CAD, but Lp(a) and OxPL-apoB were associated with multi-vessel CAD. All biomarkers were associated with CV events. Odds of multi-vessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI 1.03-1.18, P=0.006), 1.18 (95% CI 1.03-1.34, P=0.01), and 1.07 (95% CI 0.99-1.16, P=0.07), respectively ( Figure, A ). Hazard ratios for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI 1.03-1.14, P=0.001), 1.15 (95% CI 1.05-1.26, P=0.004), and 1.07 (95% CI 1.01-1.14, P=0.02), respectively ( Figure, B ). Conclusions: Lp(a) and OxPL-apoB are associated with multi-vessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident CV events.
Abstract 9770: Pulmonary Artery Pulsatility Index After Pediatric Heart Transplant
Authors: Alexa E Golbus, Charles B Bryant, Andrew J Savage, Heather T Henderson, John F Rhodes
Journal: Circulation (2022)

Background: The Pulmonary Artery Pulsatility index (PAPi) is calculated by pulmonary artery pulse pressure divided by central venous pressure and is directly proportional to right ventricular contractility and stroke volume, and indirectly proportional to pulmonary artery afterload and filling pressures. We hypothesize that PAPi will correlate with known hemodynamic parameters and predict acute kidney injury (AKI) post heart transplant (HTx). Methods: Medical records and hemodynamic data were retrospectively reviewed for patients ≤18 years old undergoing HTx at a single center between 1/2007-9/2021. Subgroups by HTx indication were myopathy or congenital heart disease (CHD). PAPi was calculated at catheterizations up to 5 years post HTx, with normal ≥ 2.0. Results: Fifty-three children underwent HTx in myopathy (n=27) or CHD (n=26) subgroups. Mean age at HTx was 5.95 ± 6.13 years (range: 58 days-18 years) with no difference between myopathy and CHD subgroups. PAPi correlated with known cardiovascular measures including thermodilution cardiac index (TDCI) and right ventricular end-diastolic pressure (RVEDp), confirming PAPi as a predictor of cardiovascular hemodynamics (Table 1) . At 1 year, children with AKI (n=11/49) had a lower PAPi compared to those with no AKI (1.55 ± 0.43 vs. 2.50 ± 1.16; p=0.004). Comparing initial to 5-year PAPi, the myopathy subgroup (n=18) remained similar (2.10 ± 0.99 vs. 2.12 ± 1.55; p=0.48) and the CHD subgroup (n=12) declined significantly (2.12 ± 0.91 vs. 1.67 ± 0.55; p=0.04). Conclusions: The PAPi in children post HTx correlates with known hemodynamic parameters. PAPi serves as a marker predicting renal dysfunction 1 year post HTx. Between HTx and 5 years post HTx, PAPi did not improve for the myopathy subgroup and declined significantly for the CHD subgroup suggesting that incorporating PAPi into existing risk models may substantially improve earlier implementation for advanced therapies and thus improve clinical outcomes.
Abstract 317: Brain MRI And Spectroscopy Biomarkers Predict Outcome After Pediatric Cardiac Arrest In POCCA
Authors: Ericka L Fink, Patrick M Kochanek, Stefan Bluml, Jessica Wisnowski, Srikala Narayanan, subramanian subramanian, Sue Beers, Rachel Berger, Hulya Bayir, Chunyan Wang, Jose Pineda, Alexis A Topjian, aline maddux, Frederick Willyerd, Elizabeth A Hunt, Melissa G Chung, Christopher Newth, Lincoln Smith, Lesley Doughty, J. Wesley Diddle, Juan Piantino, Karen H Walson, Binod Balakrishnan, stuart friess, Ashley Siems, Craig Press, Jason Patregnani, Michael T Meyer, Tamara Haller, Amery Treble-Barna, Robert Clark, Anthony Fabio, Ashok Panigrahy
Journal: Circulation (2022)

Conventional (T2) and diffusion-weighted imaging (DWI) on brain magnetic resonance imaging (MRI) and lactate and N-acetyl-aspartate (NAA) on MR spectroscopy (MRS) can characterize brain hypoxic-ischemic injury. We hypothesized these neuroimaging biomarkers would be associated with 1 year outcome after pediatric cardiac arrest in a multicenter, observational study. Fourteen US centers enrolled children aged &lt; 18 years with pediatric intensive care unit admission post-arrest if pre- arrest Pediatric Cerebral Performance Category score was 1-3. Brain MRI/MRS performed within 2 weeks post-arrest were analyzed independently by 2 pediatric neuroradiologists blinded to outcome. MRI lesions on T2 and DWI were scored by region and severity (0=none, 1=mild, 2=moderate, 3=severe). Total MRI score was a sum of T2 and DWI lesions in gray and white matter (max 34). Lactate and NAA were measured in the basal ganglia, thalamus, and occipital-parietal white/gray matter and quantified by LCModel. Multivariate regression was performed to determine the association with unfavorable outcome (Vineland Adaptive Behavioral Scale &lt; 70 or dead at 1 year). Of 164 children, 66 and 32 had evaluable MRI and MRS data and 23 (35%) and 12 (38%) had unfavorable outcome, respectively. Children with unfavorable outcome had more unwitnessed and out-of-hospital events. DWI lesions in all 4 lobes predicted unfavorable outcome, whereas T2 temporal gray and parietal white matter lesions predicted unfavorable outcome, p&lt;0.05. T2/DWI lesions in the basal ganglia, thalamus, and centrum semi-ovale predicted unfavorable outcome, p&lt;0.05. Cerebellar/ brain stem white matter lesions predicted unfavorable outcome, p&lt;.05. Total MRI scores were markedly higher in the unfavorable group (median [interquartile range]) (22 [7, 32] vs. 1 [0,8], p&lt;0.001). Increased lactate and decreased NAA predicted unfavorable outcome in all 4 regions of interest, p&lt;0.05. In a multivariate logistic regression, MRI total score (odds ratio 1.12 [95% confidence interval 1.05, 1.20]) and witnessed event status (0.07 [0.01, 0.34]) predicted outcome. Brain MRI and MRS biomarkers are useful to identify children with unfavorable outcome within 2 weeks post-cardiac arrest.
Abstract 9607: Sex Differences in Cardiovascular Outcomes in Dialysis Patients
Authors: Silvi Shah, Annette Christianson, Karthikeyan Meganathan, Anthony Leonard, Deidra Crews, Jack Rubinstein, Mark Mitsnefes, Daniel Schauer, Charuhas Thakar
Journal: Circulation (2022)

Background: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared to the general population. Little is known about sex differences in cardiovascular outcomes in dialysis patients which precludes sex-specific therapies. Methods: We evaluated 508,822 patients who initiated dialysis between 1/1/2005 and 12/31/2014 using the United States Renal Data System with linked Medicare claims. We determined rates of hospitalizations for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with the outcome of cardiovascular events, cardiovascular death, and all-cause death, using adjusted time-to-event models. Results: The mean age of patients in the study cohort was 70±12 years, and 44.7% were women. The cardiovascular event rate was 232 PTPY (95% CI, 231-233), with a higher rate in women than in men (248 PTPY; 95% CI, 247-250 vs. 219 PTPY; 95% CI, 217-220). Women had a 13% higher risk of cardiovascular events than did men (HR, 1.13; 95% CI, 1.11-1.14). Women had a 15% higher risk of heart failure (HR, 1.15; 95% CI, 1.13-1.16), a 29% higher risk of stroke (HR, 1.29; 95% CI, 1.26-1.32), and no difference in risk of acute coronary syndrome (HR, 0.99; 95% CI, 0.97-1.01). Women had a lower risk of cardiovascular death (HR, 0.84; 95% CI, 0.83-0.85), and a lower risk of all-cause death, as compared to men (OR, 0.92; 95% CI, 0.91-0.93). Conclusion: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality. Further studies are needed to better understand the factors associated with sex differences in cardiovascular outcomes in patients with kidney failure.